Association of NOS1AP genetic variants with QT interval duration in families from the Diabetes Heart Study.

نویسندگان

  • Allison B Lehtinen
  • Christopher Newton-Cheh
  • Julie T Ziegler
  • Carl D Langefeld
  • Barry I Freedman
  • Kurt R Daniel
  • David M Herrington
  • Donald W Bowden
چکیده

OBJECTIVES Prolongation of the electrocardiographic QT interval is a risk factor for sudden cardiac death (SCD). Diabetic individuals are at increased risk for prolonged QT interval and SCD. We sought to replicate the finding that genetic variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with QT interval duration in a type 2 diabetes-enriched sample of European ancestry. RESEARCH DESIGN AND METHODS Two single nucleotide polymorphisms (SNPs) in NOS1AP were genotyped in 624 European Americans and 127 African Americans from 400 pedigrees enriched for type 2 diabetes. An additive genetic model was tested for each SNP in ancestry-specific analyses in the total sample and the diabetic subset (European Americans, n = 514; African Americans, n = 115), excluding from the analyses individuals taking QT-altering medications. RESULTS In European Americans, rs10494366 minor homozygotes had a 9.3-ms-longer QT interval compared with major homozygotes (P = 5.7 x 10(-5)); rs10918594 minor homozygotes had a 12.5-ms-longer QT interval compared with major homozygotes (P = 1.5 x 10(-6)). Restricting analyses to the diabetic European Americans strengthened the effect despite the reduction in sample size (11.3-ms difference, P = 5.1 x 10(-5); 13.9-ms difference, P = 1.6 x 10(-6), respectively). No association between the NOS1AP SNPs and QT interval duration was observed in the limited number of African Americans. CONCLUSIONS Two NOS1AP SNPs are strongly associated with QT interval duration in a predominately diabetic European-American sample. Stronger effects of NOS1AP variants in diabetic individuals suggest that this patient subset may be particularly susceptible to genetic variants that influence myocardial depolarization and repolarization as manifest in the QT interval.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Original Article: Genetics A common variant of NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes

Aims Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes. Methods Three single nuc...

متن کامل

Common NOS1AP variants are associated with a prolonged QTc interval in the Rotterdam Study.

BACKGROUND QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden car...

متن کامل

A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project.

BACKGROUND We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations. METHODS AND RESULTS We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common va...

متن کامل

Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this ...

متن کامل

Associations between genetic variants in the NOS1AP (CAPON) gene and cardiac repolarization in the old order Amish.

BACKGROUND Through a genome-wide association study, we discovered an association of the electrocardiographic QT interval with polymorphisms in the NOS1AP (CAPON) gene. The purpose of the current study was to replicate this association in the Old Order Amish. METHODS Four NOS1AP SNPs were selected that captured all major haplotypes in the region of interest ( approximately 120 kb segment). Gen...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Diabetes

دوره 57 4  شماره 

صفحات  -

تاریخ انتشار 2008